This grant is requested to support a program in basic research directed at elucidating, at a molecular level, the nature and mode of functioning of the adrenergic receptors for catecholamines. Catecholamies such as norepinephrine and epinephrine are of vital importance in the hormonal control of the entire circulation. These compounds appear to act via stimulation of adenyl cyclase in cell membranes which is in turn mediated by binding to specific beta-adrenergic receptors. The specific aims of these studies include: 1) the isolation, purification and characterization of adrenergic receptors from heart muscle and other tissues, and 2) delineation of the way in which receptors interact with adenyl cyclase, and 3) study of the isolated receptors in disease states. These aims will be achieved by studying the binding of radioactively labeled (negative) 3H alprenolol, a competitive beta-adrenergic antagonist, to cell membrane fragments isolated from heart muscle, and to specific proteins isolated and purified from these membranes. Detailed characterization of these receptor structures will ultimately permit evaluation of possible alterations in their structure and function in disease states such as hypertension, congestive heart failure, or in physiological processes such as aging. BIBLIOGRAPHIC REFERENCES: Mukherjee, C. and Lefkowitz, R.J. Regulation of Beta-Adrenergic Receptors in Isolated Frog Erythrocyte Plasma Membranes. Mol. Pharmacol., 13, 291-303, 1977. Limbird, L.E. and Lefkowitz, R.J. Resolution of Beta-Adrenergic Receptors and Adenylate Cyclase by Gel Exclusion Chromatography. J. Biol. Chem. 252, 799-802, 1977.